Interleukin-4Ra Blockade by Dupilumab Decreases Staphylococcus Colonization and Increases Microbial Diversity in CRSwNP

NCT05094570 | Recruiting Phase 4 FDA Drug

• 1 other identifier: HSR210309
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Hypothesis: The investigators hypothesize that in patients with CRSwNP who demonstrate sinus colonization with staphylococcus aureus, the administration of dupilumab will be associated with decreased staph colonization and an increase in microbial diversity. Primary Objective will be to demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance while increasing microbial diversity in patients with CRSwNPs who are culture positive for staph aureus at enrollment. Secondary Objectives will be to correlate reduction in Staph aureus abundance and improved bacterial diversity with increased expression of anti-microbial proteins (ß-defensins1-4) and cathelicidin LL-37. In addition, the investigators will correlate improvements in microbial diversity/decreased staph abundance with clinical improvements as assessed via questionnaires and objective/subjective smell function and also as improvements in cellular/immune T2 inflammation as assessed by reduced expression of T2 cytokines/chemokines and eosinophil/eosinophil-derived proteins.

Conditions

Nasal Polyps; Staphylococcus Aureus

Keywords

Nasal polyps; Staph aureus; Interleukin-4/-13

Outcome Measures

Primary Outcomes (1)

• To demonstrate that dupilumab reduces staphylococcus aureus

  To demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance. The abundance of Staph aureus will be determined using qPCR of the femA gene and compared at baseline and after 16 weeks of dupilumab treatment. Statistical differences in the quantity of staph aureus (as ascertained by qPCR) will be determined utilizing data obtained from all subjects comparing data obtained at the end of the study in comparison to the beginning of the study.

  16 weeks

Secondary Outcomes (2)

• To correlate reduction in Staph aureus with improvements in clinical status

  16 weeks

• To demonstrate that dupilumab increases microbial diversity

  16 weeks

Study Arms (1)

Dupilumab treatment

EXPERIMENTAL

Treatment with dupilumab to demonstrate decreased staph prevalence and improve microbial diversity

Drug: Dupilumab Prefilled Syringe

Interventions

Dupilumab Prefilled Syringe DRUG

Dupilumab 300 mg

Also known as: DUPIXENT

Dupilumab treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of CRSwNP including subjects with AERD
• Sinonasal culture demonstrating staph aureus at visit 1
• History of FESS with patent sinus ostia sufficient to obtain culture and tissue samples from the middle meatus
• Asthma, if present, should be well controlled
• Atopic dermatitis, if present, should be well controlled
• Use of nasal saline irrigation and stable dosing (\>1 month) of topical corticosteroids is permitted
• Intent of the physicians caring to start dupilumab therapy as part of subject's standard of care
• Subject meets FDA approved criteria for the use of dupilumab for nasal polyps

You may not qualify if:

• Concurrent serious medical problem
• Uncontrolled asthma (ACT \<20 at screening visit)
• Recent (within 60 days) use of oral corticosteroids
• Recent (within 60 days) urgent care, ED visit, or hospitalization for asthma
• Current smoker or has smoked \>10 pack-years
• Biologic therapy including asthma biologic therapy in last 3 months
• Recent (within 1 month) change in CRS medical treatment (topical steroids, surfactants, irrigation protocol, etc. including changes in delivery volume or delivery methodology)
• Recent (within 6 weeks) upper respiratory infection
• Antibiotics within 6 weeks
• Pregnant or breast-feeding women
• Any contraindication to the use of dupilumab including hypersensitivity on previous administration

Sponsors & Collaborators

• University of Virginia: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Nasal Polyps; Staphylococcal Infections

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Larry C Borish, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristin W Wavell Shifflett, BS

CONTACT

4349246874; kww7d@virginia.edu

Deborah Murphy, BSN

CONTACT

4349823510; ddm9q@virginia.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine and Microbiology

Model Details: Open label, single arm

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 26, 2021
• Study Start: September 1, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)